Associations of Anxiety during the COVID-19 Pandemic with Patient Characteristics and Behaviors in CKD Patients: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: Chronic kidney disease (CKD) is associated with anxiety and depression. Although the coronavirus disease 2019 (COVID-19) pandemic has increased stressors on patients with CKD, assessments of anxiety and its predictors and consequences on behaviors, specifically virus mitigation behaviors, are lacking. Methods: From June to October 2020, we administered a survey to 1873 patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, asking participants about anxiety related to the COVID-19 pandemic. We examined associations between anxiety and participant demographics, clinical indexes, and health literacy and whether anxiety was associated with health-related behaviors and COVID-19 mitigation behaviors. Results: The mean age of the study population was 70 years (SD=9.6 years), 47% were women, 39% were Black non-Hispanic, 14% were Hispanic, and 38% had a history of cardiovascular disease. In adjusted analyses, younger age, being a woman, Hispanic ethnicity, cardiovascular disease, household income <$20,000, and marginal or inadequate health literacy predicted higher anxiety. Higher global COVID-19-related anxiety scores were associated with higher odds of reporting always wearing a mask in public (OR=1.3 [95% CI, 1.14 to 1.48], P<0.001) and of eating less healthy foods (OR=1.29 [95% CI, 1.13 to 1.46], P<0.001), reduced physical activity (OR=1.32 [95% CI, 1.2 to 1.45], P<0.001), and weight gain (OR=1.23 [95% CI, 1.11 to 1.38], P=0.001). Conclusions: Higher anxiety levels related to the COVID-19 pandemic were associated not only with higher self-reported adherence to mask wearing but also with higher weight gain and less adherence to healthy lifestyle behaviors. Interventions are needed to support continuation of healthy lifestyle behaviors in patients with CKD experiencing increased anxiety related to the pandemic.

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. METHODS: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. RESULTS: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. CONCLUSIONS: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.

Identification of Distinct Clinical Subphenotypes in Critically Ill Patients With COVID-19.

BACKGROUND: Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies. RESEARCH QUESTION: Can unique subphenotypes be identified among critically ill patients with COVID-19? STUDY DESIGN AND METHODS: Using data from a multicenter cohort study that enrolled critically ill patients with COVID-19 from 67 hospitals across the United States, we randomly divided centers into discovery and replication cohorts. We used latent class analysis independently in each cohort to identify subphenotypes based on clinical and laboratory variables. We then analyzed the associations of subphenotypes with 28-day mortality. RESULTS: Latent class analysis identified four subphenotypes (SP) with consistent characteristics across the discovery (45 centers; n = 2,188) and replication (22 centers; n = 1,112) cohorts. SP1 was characterized by shock, acidemia, and multiorgan dysfunction, including acute kidney injury treated with renal replacement therapy. SP2 was characterized by high C-reactive protein, early need for mechanical ventilation, and the highest rate of ARDS. SP3 showed the highest burden of chronic diseases, whereas SP4 demonstrated limited chronic disease burden and mild physiologic abnormalities. Twenty-eight-day mortality in the discovery cohort ranged from 20.6% (SP4) to 52.9% (SP1). Mortality across subphenotypes remained different after adjustment for demographics, comorbidities, organ dysfunction and illness severity, regional and hospital factors. Compared with SP4, the relative risks were as follows: SP1, 1.67 (95% CI, 1.36-2.03); SP2, 1.39 (95% CI, 1.17-1.65); and SP3, 1.39 (95% CI, 1.15-1.67). Findings were similar in the replication cohort. INTERPRETATION: We identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality.